‘Many, if not most, will eventually get infected’: Gagandeep Kang

Shriya Mohan | Updated on April 03, 2020 Published on April 03, 2020

The Clinician scientist on vaccines being tested for Covid-19, and whether a lockdown is really what India needs

The Covid-19 infections worldwide are racing toward the one-million mark, and more than 2,000 have tested positive in India. As the pandemic courses through countries rapidly, the scientific community is working at a breakneck pace to produce a vaccine that could generate a fitting human immune response. Clinician scientist and Fellow of the Royal Society, Gagandeep Kang is the vice-chair of the Coalition for Epidemic Preparedness Innovations (CEPI), a global alliance that has backed eight potential vaccines against the virus. Kang tells BLink about the vaccine trials and how the focus will be on slowing the spread of Covid-19.

Is it only a matter of time before we all test Covid-19 positive?

Sooner or later, a lot of people will test SARS-CoV2 positive. Respiratory viruses spread easily and, in this first round, the estimates are that, without any mitigation steps, 20-80 per cent of the world will be infected. At the individual level, it isn’t a bad thing for survival, because you will make antibodies and you’ll have one to two years of protection, at the very least. For SARS (Severe Acute Respiratory Syndrome), antibodies were found even 10 years after an infection. But the problem with an infection is that you can’t predict who will do well and who won’t, even though generally older people and those with other illnesses do worse (than the others).

The rates of mortality with this are higher than those for seasonal influenza. If you could stretch out infections in a large part of the population over five or 10 years, then it wouldn’t be so bad because the healthcare system would not be stretched or overwhelmed with many severe cases, as we are seeing in other parts of the world. The problem with this is the compression into a short time.

Could you tell us about the eight potential vaccines for this virus the CEPI has managed to get off the ground?

As the vice-chair of CEPI, I’m on its Board. The work is being done by the CEPI staff. Richard Hatchett, the CEO of CEPI, is a prescient and thoughtful physician and leader. In January, when the genetic sequence of the virus was known, Richard called an emergency meeting to request for authority to go ahead and fund vaccine development, to which, of course, we unanimously agreed.

The first three grants went out within three weeks of the virus being identified and the sequence of the virus being known. The fourth grant went out in January. Subsequently, there have been four other grants. The first vaccine that CEPI funded, Moderna, is based on the mRNA (messenger ribonucleic acid) approach and it went to human trials in March. It is now being funded by The National Institute of Allergy and Infectious Diseases, US. The only other vaccine that went to human trials last month is a Chinese vaccine based on proteins as virus-like particles.

CEPI has helped fund two more vaccines that are going to human trials in April. It doesn’t matter whether CEPI’s vaccine candidates succeed or not; CEPI is going to support whoever needs help to push a vaccine forward. We have never seen this pace and this kind of collaboration before.

How is the mRNA approach different from the way vaccines are normally developed?

The way you make a vaccine usually is to take the whole virus or a component of it and put it inside a human being so that the immune system sees the virus and responds to it. With mRNA, what you’re doing is taking the genetic sequence of the virus that encodes for one or more of the proteins that make up the virus. Essentially, messenger RNA carries the sequence for the viral proteins into a cell. The cell makes the proteins and releases them outside. And the immune system recognises a foreign protein and makes an immune response.

For humans, this is not the first time we’re trying an mRNA vaccine. Moderna has vaccinated over 2700 people with other mRNA vaccines and other smaller companies have been trying this approach for cancer and some infectious diseases. Nothing has got into humans as yet as a licensed product. Part of the reason is that regulators want safety studies, then immunogenicity and dose-ranging studies and finally efficacy studies. Progress tends to be slow because it is sequential. In this case they are making sure that progression happens as rapidly as possible.

What about mutations that people fear?

This virus is very stable. A virus mutates and keeps the mutations if they are useful to the virus. What would be a useful mutation to a virus? A mutation that allows it to evade the immune response. If you have a virus that no human in the world is immune to, why would it need to mutate and keep those mutations? There is no selection pressure on this virus because only infected people are immune, and that is still a small fraction of the world’s population.

This is a virus we still know very little about. Have we got to know it better in the past month?

Yes, we have. Ten days ago, we had a publication on the interactome (protein interaction study) of the virus. It has been identified that 26 of the 29 proteins of the virus interact with every human protein. A total of 332 virus protein-human protein interactions were identified and 66 human proteins or targets were found for which there are already 69 approved compounds that could potentially be developed into drugs. We haven’t been able to get this sort of information this fast before.

A new finding suggests that plasma transfusions from recovered patients help those with acute infections. This is potentially good for treatment as well as vaccine development.

A somewhat worrying finding, on the other hand, is the potential for antibody dependent enhancement similar to what is seen in dengue, which means if vaccinated people are exposed to the virus later, they may get a more severe disease. You don’t want to create a solution that creates an added problem. Every day we discover more and there is just so much for everyone to do until we have better understanding and solutions for treatment and prevention.

Does the lockdown approach work for India? A lot of experts believe that India needs a more community participative approach…

This is not going to be controlled without community participation because ultimately control is based on individual behaviour. But when has our community listened to an urgent message? What will convince people that it (the virus) needs to be taken seriously? Whatever it is, we need to do that.

Stay away from people who can infect you and, if you are infected, stop infecting others. It’s simple.

Asymptomatic and pre-symptomatic people (those without symptoms, or pre-symptoms) are a variable proportion of the infected. You can’t expect an asymptomatic person to go get tested. But if you have a cold and cough, can you avoid being around people for two weeks? And get tested if you have symptoms?

If every individual actually takes responsibility for themselves as well as for the people around them, we would slow the spread.

Many, if not most, people will eventually get infected. It’s just a question of how you stretch out the amount of time and economic costs. What we’re trying to do is slow down the virus so that our healthcare systems can handle the percentage of people who will get very sick.

Are we testing enough? How should we lower costs of testing kits?

No question about it, right now we are not testing enough to slow the spread. You need to do tests to identify cases, to isolate them, and quarantine their contacts for two days before they became ill. Everybody is focussed on the costs of tests and the costs to the healthcare system and how much this is going to cost the budget. Can we stop spending so much on the army for one year and spend on this war instead? We will have better overall outcomes for people if we invest in health.

How long are we in this for?

Everybody is predicting between 12 and 18 months, depending on the control measures we put in place. The virus isn’t going to disappear in that time. We will only have better strategies for treatment and for longer-term control.

Shriya Mohan

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Published on April 03, 2020
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